A Phase 2 Study of ⁹⁰Y-Ibritumomab Tiuxetan (⁹⁰Y-Zevalin®) in Relapsed/Refractory Non-Hodgkin’s Lymphoma: Preliminary Report of the Argentinean Cooperative Group.

Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in <1 year progression-free survival. ⁹⁰Y-Zevalin® (⁹⁰Y-ibritumomab tiuxetan), a radiolabeled antibody to CD20, has shown promising activity in this patient population. We present the initial outcome of a phase 2 trial conducted by the Argentinean Cooperative Group, using ⁹⁰Y-Zevalin for relapsed refractory FL and transformed lymphomas.

Methods. Between September 2005 and November 2005, we recruited 10 patients (pts; 6 male/4 female; median age = 56 yr [range: 45–71 yr]) with platelets >100,000/mm³ and bone marrow involvement <25% for this trial. Nine pts had FL and 1 pt had mantle cell lymphoma. Four pts had bulky disease (largest diameter >5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m² IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) ⁹⁰Y-Zevalin per kg or 15 MBq (0.4 mCi) ⁹⁰Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria.

Results. Five pts received a complete dose of 0.4 mCi ⁹⁰Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi ⁹⁰Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment.

Conclusion. The use of ⁹⁰Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients.